It has been demonstrated that CD8 positive cytotoxic T lymphocytes (CTLs) recognize epitope peptides derived from the tumor-associated antigens (TAAs) found on major histocompatibility complex (MHC) class I molecules, and then kill the tumor cells. Since the discovery of the melanoma antigen (MAGE) family as the first example of TAAs, many other TAAs have been discovered, primarily through immunological approaches (Boon T, Int J Cancer 1993 May 8, 54(2): 177-80; Boon T & van der Bruggen P, J Exp Med 1996 Mar. 1, 183(3): 725-9). Some of these TAAs are currently undergoing clinical development as immunotherapeutic targets.
Identification of new TAAs, capable of inducing potent and specific anti-tumor immune responses, warrants further development and clinical application of peptide vaccination strategies for various types of cancer (Harris C C, J Natl Cancer Inst 1996 Oct. 16, 88(20): 1442-55; Butterfield L H et al., Cancer Res 1999 Jul. 1, 59(13): 3134-42; Vissers J L et al., Cancer Res 1999 Nov. 1, 59(21): 5554-9; van der Burg S H et al., J Immunol 1996 May 1, 156(9): 3308-14; Tanaka F et al., Cancer Res 1997 Oct. 15, 57(20): 4465-8; Fujie T et al., Int J Cancer 1999 Jan. 18, 80(2): 169-72; Kikuchi M et al., Int J Cancer 1999 May 5, 81(3): 459-66; Oiso M et al., Int J Cancer 1999 May 5, 81(3): 387-94). To date, there have been several reports of clinical trials using these tumor-associated antigen derived peptides. Unfortunately, only a low objective response rate has been observed in these cancer vaccine trials so far (Belli F et al., J Clin Oncol 2002 Oct. 15, 20(20): 4169-80; Coulie P G et al., Immunol Rev 2002 October, 188: 33-42; Rosenberg S A et al., Nat Med 2004 September, 10(9): 909-15).
As a target for immunotherapy, TAAs indispensable for the proliferation and survival of cancer cells are suited, because the use of such TAAs may minimize the well-described risk of immune escape of cancer cells attributable to deletion, mutation, or down-regulation of TAAs as a consequence of therapeutically driven immune selection.
WDRPUH was identified as a novel WD repeat protein that is upregulated in hepatocellular carcinoma through gene expression profile using a genome-wide cDNA microarray containing 23,040 genes (Silva et al., Neoplasia 2005 April; 7(4):348-55, WO 2003/104276). WD repeat-containing proteins have been reported to play crucial roles in a wide range of physiologic functions, including signal transduction, RNA processing (Bjorn et al., Mol Cell Biol. 1989 September; 9(9):3698-709.), remodeling of the cytoskeleton (Vaisman et al., Mol Gen Genet. 1995 Apr. 20; 247(2):123-36), regulation of vesicular traffic (Pryer et al., J Cell Biol. 1993 February; 120(4):865-75), and cell division (Feldman et al., Cell. 1997 Oct. 17; 91(2):221-30). Northern blot analysis demonstrated that WDRPUH was over-expressed at a significantly high level in a great majority of hepatocellular carcinoma, but was not expressed in normal organs except for testis. Furthermore, suppression of WDRPUH expression by siRNA was shown to significantly inhibit growth of human hepatocellular carcinoma cell lines (Silva et al., Neoplasia 2005 April; 7(4):348-55, WO 2003/104276).